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Exploiting fly models to investigate rare human neurological disorders

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Neural Regeneration research 2025年第1期20卷 21-28页

作者： Tomomi Tanaka Hyung-Lok Chung Department of Neurology Houston Methodist Research InstituteHoustonTXUSA Department of Neurology Weill Cornell Medical CollegeNew YorkNYUSA

Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological *** attributed to genetic mutations that disrupt protein function or structure,understanding their genetic basis is crucial for accurate diagnosis and targeted *** investigate the underlying pathogenesis of these conditions,researchers often use non-mammalian model organisms,such as Drosophila(fruit flies),which is valued for their genetic manipulability,cost-efficiency,and preservation of genes and biological functions across evolutionary *** tools available in Drosophila,including CRISPR-Cas9,offer a means to manipulate gene expression,allowing for a deep exploration of the genetic underpinnings of rare neurological *** boasts a versatile genetic toolkit,rapid generation turnover,and ease of large-scale experimentation,making it an invaluable resource for identifying potential drug *** can expose flies carrying disease-associated mutations to various compounds,rapidly pinpointing promising therapeutic agents for further investigation in mammalian models and,ultimately,clinical *** this comprehensive review,we explore rare neurological diseases where fly research has significantly contributed to our understanding of their genetic basis,pathophysiology,and potential therapeutic *** discuss rare diseases associated with both neuron-expressed and glial-expressed *** cases include mutations in CDK19 resulting in epilepsy and developmental delay,mutations in TIAM1 leading to a neurodevelopmental disorder with seizures and language delay,and mutations in IRF2BPL causing seizures,a neurodevelopmental disorder with regression,loss of speech,and abnormal *** we explore mutations in EMC1 related to cerebellar atrophy,visual impairment,psychomotor retardation,and gain-of-function mutations in ACOX1 causing Mitchell ***-of-fun

关键词： ACOX1 Drosophila melanogaster glia lipid metabolism model organisms neuroinflammation neurologic disorders neuron rare disease VLCFA

Asking one mechanism in glial cells during neuroinflammation

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Neural Regeneration research 2025年第4期20卷 1077-1078页

作者： Xiaoli Guo Chikako Harada Takayuki Harada Visual research Project Tokyo Metropolitan Institute of Medical ScienceTokyoJapan

Multiple sclerosis(MS),which is characterized by inflammatory demyelination in the central nervous system(CNS),is the most common neurological disease in the young adult *** autoimmune encephalomyelitis(EAE),an animal model of MS,is often used in preclinical *** data indicate that in addition to immune cells such as T cells and dendritic cells,CNS resident microglia and astrocytes play important roles in demyelinating neuroinflammation(Healy et al.,2022).In particular,microglia are key immune-competent cells that can respond to environmental *** depletion of transforming growth factor-β-activated kinase 1,a mitogen-associated protein kinase kinase kinase,in microglia is reported to reduce CNS inflammation and diminish axonal and myelin damage *** suggests that elucidating the mechanisms of microglia-specific responses during pathologies may help in the development of treatments that reduce EAE/MS disease severity(Goldmann et al.,2013).

关键词： inflammation clinical

Monogenic gene therapy for glaucoma and optic nerve injury

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Neural Regeneration research 2025年第3期20卷 815-816页

作者： Chikako Harada Xiaoli Guo Takayuki Harada Visual research Project Tokyo Metropolitan Institute of Medical ScienceTokyoJapan

The prevalence of glaucoma, the second leading cause of global blindness, is increasing due to aging populations. In glaucoma, degeneration of the optic nerve and retinal ganglion cells(RGCs) causes visual field defec... 详细信息

关键词： visual glaucoma degeneration

Women in visual neural regeneration research

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Neural Regeneration research 2025年第2期20卷 489-490页

作者： Tonia S.Rex David J.Calkins Vanderbilt Eye institute Vanderbilt University Medical CenterNashvilleTNUSA

The year 2024 marks the 60^(th)anniversary of Title IX and 25 years since the New York Times revealed bias against female faculty members at the Massachusetts institute of *** take an opportunity here to examine the state of gender bias in a relatively new yet already prominent field,neural regeneration in the visual system,for which there is a well-defined context useful for this *** National Eye institute(NEI)provided the first round of research funding for its Audacious Goals Initiative(AGI)on visual neural regeneration in 2013 and the last round in ***,we focus on this *** sources included PubMed,the National Science Foundation(NSF),the NEI,the Blue Ridge institute for medical research and data from the major professional organization for eye and vision research,the Association for research in Vision and Ophthalmology(ARVO).

关键词： neural visual Times

Sleep as a window to understand and regulate Alzheimer's disease:emerging roles of thalamic reticular nucleus

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Neural Regeneration research 2025年第6期20卷 1711-1712页

作者： Haoqi Sun Shiqian Shen Robert J.Thomas M.Brandon Westover Can Zhang Department of Neurology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Center for Translational Pain research Department of AnesthesiaCritical Care and Pain MedicineMassachusetis General HospitalHarvard Medical SchoolBostonMAUSA Division of Pulmonary Critical Care and Sleep MedicineDepartment of MedicineBeth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Genetics and Aging research Unit McCance Center for Brain HealthMass General Institute for Neurodegenerative DiseaseDepartment of NeurologyMassachusetts General HospitalHarvard Medical SchoolBostonMAUSA

Introduction:Alzheimer 's disease(AD) is a common neurodegenerative disorder and the primary cause of dementia. Considerable evidence supports the “amyloid hypothesis,” stating that the pathogenesis of AD is primarily caused by the deposition of amyloid-β(Aβ), which drives tau phosphorylation, neuroinflammation, and neurodegeneration in the brain. The amyloid hypothesis is strengthened by the significant and moderate benefit of lecanemab, a humanized antibody through an anti-amyloid mechanism,showing slowed clinical decline(van Dyck et al.,2023). The recent positive results of anti-amyloid trials have brought back focus on the amyloid hypothesis through biochemical, genetic, and pharmacological approaches(Zhang, 2023).

关键词： Alzheimer inflammation hypothesis

Compartmentalized regulation of organelle integrity in neurodegenerative diseases:lessons from the Drosophila motor neuron

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Neural Regeneration research 2025年第1期20卷 195-196页

作者： Hyun Sung Department of Neurology Johns Hopkins University School of MedicineBaltimoreMDUSA medical research institute and Department of PharmacologyPusan National University School of MedicineYangsanRepublic of Korea

Neurons are highly polarized,morphologically asymmetric,and functionally compartmentalized cells that contain long axons extending from the cell *** this reason,their maintenance relies on spatiotemporal regulation of organelle distribution between the somatodendritic and axonal *** some organelles,such as mitochondria and smooth endoplasmic reticulum,are widely distributed throughout the neuron,others are segregated to either the somatodendritic or axonal *** example,Golgi outposts and acidified lysosomes are predominantly present in the somatodendritic domain and rarely distributed along the axon,whereas newly formed autophagosomes and synaptic vesicles are mainly distributed in the distal axon(Britt et al.,2016).

关键词： organelle regulation distribution

Therapeutic potential of exercise-hormone irisin in Alzheimer's disease

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Neural Regeneration research 2025年第6期20卷 1555-1564页

作者： Eunhee Kim Rudolph ETanzi Se Hoon Choi Genetics and Aging research Unit MassGeneral Institute for Neurodegenerative DiseaseDepartment of NeurologyMassachusetts General HospitalHarvard Medical SchoolCharlestownMAUSA McCance Center for Brain Health Massachusetts General HospitalBostonMAUSA

Irisin is a myokine that is generated by cleavage of the membrane protein fibronectin type Ⅲ domain-containing protein 5(FNDC5) in response to physical exercise. Studies reveal that irisin/FNDC5 has neuroprotective functions against Alzheimer's disease, the most common form of dementia in the elderly, by improving cognitive function and reducing amyloid-β and tau pathologies as well as neuroinflammation in cell culture or animal models of Alzheimer's disease. Although current and ongoing studies on irisin/FNDC5 show promising results, further mechanistic studies are required to clarify its potential as a meaningful therapeutic target for alleviating Alzheimer's disease. We recently found that irisin treatment reduces amyloid-β pathology by increasing the activity/levels of amyloid-β-degrading enzyme neprilysin secreted from astrocytes. Herein, we present an overview of irisin/FNDC5's protective roles and mechanisms against Alzheimer's disease.

关键词： Alzheimer's disease exercise fibronectin typeⅢdomain-containing protein 5(FNDC5) irisin

Bioelectronic medicine in modulation of cortical spreading depolarization and beyond

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Neural Regeneration research 2025年第2期20卷 481-482页

作者： Khaled Alok Timothy G.White Chunyan Li Department of Neurosurgery Donald and Barbara Zucker School of Medicine at Hofstra/NorthwellHempsteadNYUSA Translational Brain research Laboratory The Feinstein Institutes for Medical ResearchManhassetNYUSA

Bioelectronic interventions,specifically trigeminal nerve st imulat ion(TNS),have attracted considerable attention in conditions where cortical spreading depolarizations(CSDs)accompanied by compromised cerebral perfusion may exacerbate neurological *** pharmacological interventions have demonstrated initial potential in addressing CSDs,a standardized treatment approach has not yet been *** objective of this perspective is to explore emerging bioelectronic methodologies for addressing CSDs,particularly emphasizing TNS,and to underscore TNS’s capacity to enhance neurovascular coupling and cerebral perfusion.

关键词： cerebral perfusion electronic

Record-breaking bifunctional oxygen electrocatalyst accomplished by a data-driven approach for zinc-air batteries

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Journal of Energy Chemistry 2025年第1期100卷 144-145页

作者： Deviprasath Chinnadurai Zhi Wei Seh institute of Materials research and Engineering (IMRE) Agency for Science Technology and Research (A*STAR)

Rechargeable zinc-air batteries(ZABs) have recently drawn great attention in energy research due to their high theoretical capacity,low costs, and inherently safe nature [1–3]. However, the sluggish cathode reactions necessitate the development of bifunctional oxygen electrocatalysts with lower ΔE indicator values. The ΔE indicator is commonly employed to quantitatively evaluate the electrocatalytic activity of a bifunctional oxygen electrocatalyst,representing the overall overpotential from oxygen reduction reaction(ORR) to oxygen evolution reaction(OER).

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